State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & Department of Cariology and Endodontics West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.
Department of Endodontics, College of Stomatology, Chongqing Medical University, Chongqing, China.
PLoS One. 2021 Mar 26;16(3):e0233944. doi: 10.1371/journal.pone.0233944. eCollection 2021.
During tooth development, dental papilla cells differentiate into odontoblasts with polarized morphology and cell function. Our previous study indicated that the C-Jun N-terminal kinase (JNK) pathway regulates human dental papilla cell adhesion, migration, and formation of focal adhesion complexes. The aim of this study was to further examine the role of the JNK pathway in dental papilla cell polarity formation. Histological staining, qPCR, and Western Blot suggested the activation of JNK signaling in polarized mouse dental papilla tissue. After performing an in vitro tooth germ organ culture and cell culture, we found that JNK inhibitor SP600125 postponed tooth germ development and reduced the polarization, migration and differentiation of mouse dental papilla cells (mDPCs). Next, we screened up-regulated polarity-related genes during dental papilla development and mDPCs or A11 differentiation. We found that Prickle3, Golga2, Golga5, and RhoA were all up-regulated, which is consistent with JNK signaling activation. Further, constitutively active RhoA mutant (RhoA Q63L) partly rescued the inhibition of SP600125 on cell differentiation and polarity formation of mDPCs. To sum up, this study suggests that JNK signaling has a positive role in the formation of dental papilla cell polarization.
在牙齿发育过程中，牙髓乳头细胞分化为具有极化形态和细胞功能的成牙本质细胞。我们之前的研究表明，c-Jun N 末端激酶（JNK）通路调节人牙髓乳头细胞的黏附、迁移和粘着斑复合物的形成。本研究旨在进一步探讨 JNK 通路在牙髓乳头细胞极性形成中的作用。组织学染色、qPCR 和 Western blot 表明极化的鼠牙髓组织中 JNK 信号的激活。在进行体外牙胚器官培养和细胞培养后，我们发现 JNK 抑制剂 SP600125 延迟了牙胚的发育，减少了鼠牙髓乳头细胞（mDPC）的极化、迁移和分化。接下来，我们筛选了在牙髓发育和 mDPC 或 A11 分化过程中上调的极性相关基因。我们发现 Prickle3、Golga2、Golga5 和 RhoA 均上调，与 JNK 信号的激活一致。此外，组成型激活的 RhoA 突变体（RhoA Q63L）部分挽救了 SP600125 对 mDPC 细胞分化和极性形成的抑制作用。总之，本研究表明 JNK 信号在牙髓乳头细胞极化形成中具有正向作用。
